Arumugam Manoharan

Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, dalteparin (Fragmin) and heparinoid, danaparoid (Orgaran)

Summary. The incidence of cross‐reactivity between unfractionated heparin and LMWH, fragmin, in patients with HIT is significantly lower (6/15, 40%) than hitherto reported in the literature. 7/9 patients with a negative cross‐reactivity test were treated with dalteparin sodium (Fragmin) without any untoward events.

Thrombosis and bleeding in myeloproliferative disorders: identification of at-risk patients with whole blood platelet aggregation studies

Seventy‐five patients with chronic myeloproliferative disorders were studied to investigate platelet function by simultaneous measurement of platelet aggregation by the impedance method and ATP dense granule release using a whole blood platelet lumi‐aggregometer, in an attempt to identify patients at risk for thrombosis and bleeding.

Evans' syndrome, myelofibrosis and systemic lupus erythematosus: Role of procollagens in myelofibrosis

&NA; We describe an 18 yr old female with systemic lupus erythematosus presenting with Evans syndrome (autoimmune hemolytic anemia and immune thrombocytopenia) and dense myelofibrosis. Her clinical course and response to treatment were monitored with regular blood counts, serial measurements of serum procollagen I and III and periodic bone marrow examinations. This report brings to 9 the number of well‐documented cases of systemic lupus erythematosis and myelofibrosis in the literature; we discuss the pathogenesis and management of patients with this apparently rare disorder, with particular reference to the role of serum procollagen measurements as markers of myelofibrosis.

ANTITHROMBIN III DEFICIENCY IN AN AUSTRALIAN FAMILY

Antithrombin 111 is a plasma protein with an important role in thc maintenance of blood fluidity. I t inhibits blood coagulation by inactivating fhctor Xa and thrombin, the rate of neutralization being greatly increased in the presence of heparin (Kosenberg, 1975). The first case of congenital deficiency of plasma antithrombin 111 associated with recurrent Venous thrombosis was reported by Egeberg (l(J6). Since then, a number of families with more than Otle affected member have been described, the i n h e r i t h e of thc deficiency appearing to be autosonla1 dominant (Van Der Meer et at, 1073; Marciniak ct al, 1974; Filip et 01, 1976; Mackie et al, 1978). In most of thc families, affected subjects have shown a reduced amount ofantigenic material in the plasma reacting with an antiserum to antithrombin III. However, patients have been described with normal plasma concentrations of an antithrombin with reduced functional activity (Sas et al, 1974). These abnormal forms of antithrombin may be detected wit11 functional assays and also by the technique of crossed immunoelectropliorcsis (Sas et al, 1975). We have investigated 43 of 51 living members of an Australian family of English ancestory with coilgenital antithrombin I11 deficiency. Eight affected niembcrs have been detected in three generations and the abnormality is inherited as an autosoma1 dominant trait (Fig 1). Two members ofthe family (1.5 and 11.8) have died from pulmonary embolism, one after an injury and the other after an operation for stripping of varicose veins. Six of the eight affected members have suffered from multiple episodes of venous thrombosis and pulmonary embolism has occurred in three of the six. However, two affected members in generation I are more than 70 years of age and remain well apart from chronic venous insufficiency in the legs; they arc not taking oral anticoagulants. The two affected subjects without a history of thrombosis are age 17 and 16 years (subjects 111.15 and 111.33). No member of this family ivho has been shown to have a normal plasma antithrombin concentration has a convincing history of venous thrombosis.

Pure red cell aplasia of pregnancy: a distinct clinical entity

Summary. We describe a 31‐year‐old patient with pure red cell aplasia of pregnancy, successfully managed with regular blood transfusions. In vitro studies showed specific inhibition of day 14 erythroid colonies (BFU‐E) using serum and purified immunoglobulin G (IgG) obtained from the patient at diagnosis (before blood transfusion). The inhibition of BFU‐E disappeared when haematological remission occurred 3 weeks after delivery and she remains clinically well with a normal haemoglobin 4 years later.

Low‐dose combination chemotherapy for acute myeloid leukemia in elderly patients: A novel approach

Eighteen patients aged 60‐84 years with acute myeloid leukemia were treated with low‐dose combination chemotherapy comprising cytarabine, etoposide, and mitozantrone or 6‐thioguanine; seven of these patients had a pre‐existing myelodysplastic syndrome. Nine patients achieved a complete remission, and five had a partial remission. The duration of survival in these 14 responding patients has ranged from 2+ to 19+ months. Myelotoxicity occurred regularly, with time to recovery (neutrophils ≥0.5 × 109/L, platelets ≥50 × 109/L) from nadir being 10‐14 days in 12 of the 14 patients. This novel approach with an overall response rate of 78% appears to be a simple and effective form of therapy for elderly patients. Am. J. Hematol. 55:115‐117, 1997.

Methysergide-Induced Retroperitoneal Fibrosis: Successful Outcome and Two New Laboratory Features

A 25-year-old woman sought medical attention because of iliocaval manifestations of retroperitoneal fibrosis while she was taking methysergide. Laboratory studies yielded substantially increased serum procollagen III levels and anticardiolipin antibodies accompanied with anti-beta(2) glycoprotein I, findings not previously described with this disorder. Clinical and laboratory manifestations resolved after cessation of methysergide therapy.

Gentle yet effective treatment for elderly patients with refractory or relapsing multiple myeloma

Fourteen patients, aged 65–85 years, with refractory (11) or relapsing (3) multiple myeloma were treated with a “protracted‐sequential” protocol comprising vincristine 1–2 mg or vindesine 3 mg/M2 (max. 5 mg) IVI over 4 hr on D1, prednisolone 40–50 mg PO D1–14, and melphalan 2–4 mg PO or cyclophosphamide 50–100 mg PO D15–28; cycles were repeated at 4–6 weekly intervals. Treatment was continued for 12 months if the response was optimal or indefinitely if the response was suboptimal. Five patients responded optimally; their survival from the commencement of this protocol ranged from 30 to 120 months. The other nine patients achieved a partial response, their survival ranging from 4+ to 79 months. The treatment is simple, nontoxic, and as convenient as the “classic combination” of melphalan and prednisolone. Am. J. Hematol. 65:81–82, 2000.

Primary extranodal non-hodgkin's lymphoma

&NA; Summary A total of 52 of 238 patients (22%) with non‐Hodgkins lymphoma presented with disease in a primary extranodal site. The gastrointestinal‐tract was the commonest site involved (50%) and diffuse large cell was the commonest histological sub‐type of the lymphoma (64%). Survivorship analysis of these patients, treated predominantly with chemotherapy, suggests that long‐term survival is associated with: (1) low‐grade malignancy—median survival > 120 months; (2) localized disease or spread of disease confined to the regional lymph nodes—median survival 65.5 months; and (3) the use of aggressive combination chemotherapy for intermediate grade malignancy when the disease is localized or spread is confined to the regional lymph nodes—median survival > 110 months.

Response to Vermorken et al ‐ curcumin and free light chains

To the editor: We thank Vermorken et al. for their interesting comments. As suggested by Hutchison and Landgren [1], the relationship between chronic inflammation and cancer is well established, although not fully understood. Measurement of inflammatory cytokines provides clinicians with a valuable tool to use across a number of clinical settings. These authors hypothesize that measuring polyclonal free light chains (FLCs) in the serum might gain new insight into the activity of the adaptive immune system potentially allowing FLC measurement to serve as a novel clinically relevant biomarker. c-reactive protein (CRP), measured as a marker of inflammation, reflects only the activity of the innate immune system. Vermoken et al. have suggested that absolute levels of FLCs rather than their ratio may be potential biomarkers of immune stimulation and inflammation [2]. Currently, only one commercial assay is available for the measurement of serum FLCs. The assay, Freelite, consists of two assays—one to measure K FLC’s and the other to measure L FLC’s. One of these measures is an assessment of monoclonal FLCs [involved FLC (iFLC)] and the other is an assessment of polyclonal FLC’s [uninvolved FLC (uiFLC)]. In our study [3], FLC was monitored as a marker of response to curcumin. Curcumin has been known for centuries in India as an anti-inflammatory agent and it is possible to speculate that the observed response to curcumin might be associated with an anti-inflammatory effect. We are, unfortunately, not in possession of data on IL-6, CRP, or erythrocyte sedimentation rate (ESR); however, we can elaborate on the findings of the uiFLC response. From Table VII (a and b—see Supporting Information on line material), it can be seen that in patients who had an abnormal ratio at baseline (Table VIIa), at both the 4g and 8g dose of curcumin, all three markers of FLC response (i.e., rFLC, dFLC, and iFLC) decreased. However, the uiFLC increased in response to curcumin at both doses with this increase reaching significance at 8g. This data is suggestive of a decrease in the number/activity of abnormal monoclonal secreting cells and a concomitant increase in the normal polyclonal secreting cells/activity. Patients with a normal ratio at baseline (Table VIIb) show a smaller response in all measured parameters (except the iFLC at 8g) at both doses. From these findings, it can perhaps be suggested that patients with an abnormal ratio at baseline may be the subgroup who could benefit from curcumin treatment.